The objective of our research is the definition of the basic biochemical structure of the glycoprotein products of the H-2 major histocompatibility complex (MHC) as a basis for understanding in molecular terms the biological and genetic properties of this complex system. The major goal is to provide a description of the intramolecular organization and biochemical and structural properties of the allelic products of the H-2K and H-2D genes. Radiochemical and classical microsequence techniques will be used for structural analysis of selected H-2K and H-2D products to approach the questions of the intramolecular organization of these antigenic glycoproteins, and their genetic variability and evolutionary relationships with other products of the mouse MHC as well as from the MHC of other species. The studies are planned with purified material from cell lines as well as material isolated from radiolabeled spleen cells by detergent extraction and immunological precipitation. Structural analysis of the gene products from H-2 mutants and from somatic cell variants when available will be used to probe the basis of mutations and to relate molecular properties to biological reactivity such as mixed lymphocyte reactivity (MLR) and cell mediated cytotoxicity (CMC). We will continue experiments directed toward the isolation of somatic cell variants carrying structural mutations in their H-2 genes. Studies will also be initiated to develop methods for obtaining large amounts of homogeneous antibodies of restricted specificity directed against H-2 alloantigens. Such antisera would be useful for more precise serological definition as well as immunochemical and biological analyses of H-2 products.